Impact of Biomimicry in the Design of Osteoinductive Bone Substitutes: Nanoscale Matters

Abstract

Bone apatite consists in carbonated calcium deficient hydroxyapatite nanocrystals (CDHA). Biomimetic routes allow fabricating synthetic bone grafts that mimic biological apatite. In this work, we explored the role of two distinctive features of biomimetic apatites, namely nanocrystal morphology (plate vs. needle-like crystals) and carbonate content on the bone regeneration potential of CDHA scaffolds in an in vivo canine model. Both ectopic bone formation and scaffold degradation were drastically affected by the nanocrystal morphology after intramuscular implantation. Fine-CDHA foams with needle-like nanocrystals, comparable in size to bone mineral, showed a markedly higher osteoinductive potential and a superior degradation than chemically identical Coarse-CDHA foams with larger plate-shaped crystals. These findings correlated well with the superior bone healing capacity showed by the Fine-CDHA scaffolds when implanted intraosseously. Moreover, carbonate doping of CDHA, which resulted in small plate-shaped nanocrystals, accelerated both the intrinsic osteoinduction and the bone healing capacity, and significantly increased the cell-mediated resorption. These results suggest that tuning the chemical composition and the nanostructural features may allow the material to enter the physiological bone remodelling cycle, promoting a tight synchronization between scaffold degradation and bone formation.

Comparative evaluation of the physicochemical properties of nano-hydroxyapatite/collagen and natural bone ceramic/collagen scaffolds and their osteogenesis-promoting effect on MC3T3-E1 cells

“…The XPS analysis further verified that TCP phases only existed in NBC, illustrating that during the process of calcination the bovine bone might have decomposed into TCP and HA [30]. It has been reported that apatite in natural bone is a type of HA with an imperfect crystal structure, closer to that of calcium-deficient HA which has a Ca/P of about 1.5, similar to Ca/P in TCP [49, 50]. Moreover, it has been reported in the literature that, in vivo , NBC degrades and resolves faster than HA due to the high biodegradation rate and solubility of β-TCP [51].…”

CTP‐CM enhances osteogenic differentiation of hPDLSCs via NF‐κB pathway

“…TCP with ideal biocompatibility and osteoconductivity is a degradable ceramic that is rapidly absorbed and releases calcium and phosphate ions to induce bone formation in the body (Park et al, 2018). In recent studies, calcium phosphates obtained at low temperature had structural features and composition characteristics, which were much closer to the mineral phase of bone, and could enhance the osteoinductive and osteogenic properties (Barba et al, 2017, 2019). HA is the main component of human bone and accounts for approximately 70% (Holzwarth, 2011).…”

Comprehensive In Vitro Testing of Calcium Phosphate-Based Bioceramics with Orthopedic and Dentistry Applications

“…The same animal models are used for testing whether the scaffold architecture matters or not for the biological output. Data from implant testing and bone-specific animal models showed that, beyond chemical composition, the osteoinductive properties of bioceramic-based bone graft substitutes depend on gross architecture (e.g., 3D printing versus nanostructured scaffolds [217], the thickness and size of macropores [218], or the nanoarchitecture of the scaffold [219]). Osteoregeneration and biomechanical properties are improved by tailoring of pore sizes [220] or even adjusting the shape and distribution of HA crystals [221].…”